Protective effects of syringic acid,resveratrol and their combination against isoprenaline administered cardiotoxicity in wistar rats

ObjectiveTo evaluate the cardio-protection of syringic acid (SA) in combination with resveratrol (RV) in isoproterenol (ISO) induced myocardial infarcted (MI) rats.MethodsGroups of all rats were subjected oral pre-treatment at the beginning of the study with SA (50 mg/kg), RV (50 mg/kg) and combination (COMB) of SA (25 mg/kg) and RV (25 mg/kg) along with gallic acid (GA) (50 mg/kg) for 30 days. After sacrification, homogenate of heart tissue along with serum were utilized for further biochemical investigations. The effects on creatine kinase (CK), aspartate transaminase (AST), alanine transaminase (ALT) and gamma glutamyl transferase (GGT) were studied in serum and heart tissues. Glutathione-s-transferase (GST), glutathione peroxidase (GPX) and reduced glutathione (GSH), membrane bound enzymes and electrolytes were tested in heart tissues. Body weights and heart weights were also observed along with high sensitivity C-reactive protein (hs-CRP), uric acid and total protein content (TPC) in serum.ResultsCK, AST, ALT and GGT levels in serum were augmented significantly while these enzymes are decreased in cardiac tissue samples of ISO–treated rats. GST, GPX, GSH, Na⁺/K⁺, Mg²⁺, Ca²⁺ ATPases, K⁺ ions were significantly decreased while Na⁺ and Ca²⁺ ions were increased in the heart tissues of ISO-injected rats. Loss and gain of body and heart weights were noticed significantly in rats having ISO administration. ISO group showed significant increase in hs-CRP and Uric acid while significant decrease in TPC. All of actions of ISO were ameliorated by COMB.ConclusionsCOMB suppressed ISO induced MI in rats and exhibited cardio-protection.     

Molecular docking analysis of syringic acid with proteins in inflammatory cascade

Syringic Acid (SA) is a dimethoxybenzene derived from plants. Dietary SA possesses anti-obesity, anti-inflammatory and anti-steatotic effects and is of interest as a potential therapeutic medication in the treatment of obesity, diabetes, diabetic cataracts and asthma. It has anti-tumorigenic effect against hepatocellular carcinoma, lung carcinoma and oral mucosal carcinoma. It is also believed to have a protective effect on Acetaminophen induced damage in Wistar rats. Therefore, it is of interest to document the molecular docking analysis of syringic acid with proteins in inflammatory cascade such as TNF α, NFκB, P50, P65 and IKB for further consideration in drug discovery.     

Catechol thioethers with physiologically active fragments: Electrochemistry,antioxidant and cryoprotective activities

A number of asymmetrical thioethers based on 3,5-di-tert-butylcatechol containing sulfur atom bonding with physiologically active groups in the sixth position of aromatic ring have been synthesized and the electrochemical properties, antioxidant, cryoprotective activities of new thioethers have been evaluated. Cyclic voltammetry was used to estimate the oxidation potentials of thioethers in acetonitrile. The electrooxidation of compounds at the first stage leads to the formation of o-benzoquinones. The antioxidant activities of the compounds were determined using 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) assay, experiments on the oxidative damage of the DNA, the reaction of 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) induced glutathione depletion (GSH), the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro, and iron(II) chelation test. Compounds 1–9 have greater antioxidant effectiveness than 3,5-di-tert-butylcatechol (CatH₂) in all assays. The variation of physiologically active groups at sulfur atom allows to regulate lipophilic properties and antioxidant activity of compounds. Thioethers 3, 4 and 7 demonstrate the combination of radical scavenging, antioxidant activity and iron(II) binding properties. The researched compounds 1–9 were studied as possible cryoprotectants of the media for cryopreservation of the Russian sturgeon sperm. Novel cryoprotective additives in cryomedium reduce significantly the content of membrane-permeating agent (DMSO). A cryoprotective effect of an addition of the catechol thioethers depends on the structure of groups at sulfur atom. The cryoprotective properties of compounds 3, 4 and 7 are caused by combination of catechol fragment, bonded by a thioether linker with a long hydrocarbon chain and a terminal ionizable group or with a biologically relevant acetylcysteine residue.     

Phenylpropanoid acid esters from Korean propolis and their antioxidant activities

Ten phenylpropanoic acid esters were isolated from an ethanolic extract of Korean propolis. Their structures were elucidated by spectroscopic methods including NMR and ESI-MS. Caffeic acid esters with catechol moiety exhibited significant ABTS and DPPH radical scavenging activity and protective effect against DNA damage by a Fenton reaction.     

Synthesis and antioxidant activity of new lipophilic dihydropyridines

Dihydropyridines (DHPs) obtained from Hantzsch multicomponent reactions are an important pharmaceutical class of compounds marketed as antihypertensive (e.g., nifedipine, nitrendipine, and amlodipine) drugs. This study synthesized new symmetrical and unsymmetrical long-chain fatty DHPs using multicomponent reactions under metal-free conditions with sulfamic acid as a catalyst. The DHPs were tested for antioxidant activity using three different methods. The insertion of a long chain into the DHP core contributed to antioxidant potential, and compounds derived from nitro aldehydes have better antioxidant potential than the antihypertensive drug nifedipine. In addition, fatty analogs to nifedipine derived from palmitic and oleic chains showed similar antioxidant activity to the common standards butylated hydroxytoluene and vitamin E. These results showed that our new synthesized products may find novel applications as antioxidant additives or for tools for use in drug discovery.     

Synthesis and antioxidant properties of substituted 3-benzylidene-7-alkoxychroman-4-ones

A series of 3-benzylidene-7-alkoxychroman-4-one derivatives were synthesized and evaluated for their antioxidant activities. The antioxidant activity was assessed using three methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and thiobarbituric acid reactive substances (TBARS) assays. 3-Benzylidene-7-alkoxychroman-4-one derivatives bearing catecholic group on benzylidene moiety exhibited excellent antioxidant activity. Compounds having catechol moiety exhibited potent antioxidant activities in all tested methods and they were more active than the reference drug, Trolox.     

异鼠李素和异鼠李素-3-O-葡萄糖苷的抗氧化活性分析

槲皮素类化合物是众多黄酮类中活性最高的化合物之一,在医药方面有很强的药效功效。本研究选取两种槲皮素类黄酮化合物异鼠李素和异鼠李素-3-O-葡萄糖苷作为目标化合物,运用Gaussian 09软件密度泛函(DFT)方法从分子总能量、OH解离焓(BDE)的理论表征、前线分子轨道及其轨道能级、原子的净电荷布居等方面研究异鼠李素和异鼠李素-3-O-葡萄糖苷的抗氧化活性。结果表明,异鼠李素活性大于异鼠李素-3-O-葡萄糖苷,两类分子4'位的酚羟基失去氢之后对抗氧化活性的整体影响是最大的,酚羟基在这个位置上就具有较明显的高活性特征,分子中引入的糖苷不参与前线分子轨道的形成,不具有消除自由基活性的作用,但它对于分子本身的极性有很大的影响,可以改变分子在机体反应时的溶解度和吸收度。这对进一步深入研究槲皮素类黄酮化合物的抗氧化活性以及抗氧化剂的结构改良等提供了重要的科学依据。     

Synthesis of novel bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-dione) and its derivatives: Evaluation of their antioxidant properties

One pot cyclocondensation reaction of barbituric/thiobarbituric acid with aromatic aldehydes and p-phenylenediamine/2,6-diaminopyridine by refluxing in glacial acetic acid afforded novel bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-diones)/pyrido bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-diones. All the synthesized compounds were screened for their antioxidant activities using FRAP and DPPH methods. Compounds with chloro substituents showed relatively good antioxidant properties.     

Physicochemical study of floranol, its copper(II) and iron(III) complexes, and their inhibitory effect on LDL oxidation

The antioxidant activity of floranol (3,5,7,2'-tetrahydroxy-6-methoxy-8-prenylflavanone), a new flavonoid isolated from the roots of Dioclea grandiflora, was evaluated by the inhibition of human low-density lipoprotein (LDL) oxidation. Floranol increased its oxidation lag-phase significantly in a dose-dependent manner. As the antioxidant mechanism may involve metal coordination, we have undertaken a detailed study of floranol interactions with Cu(II) and Fe(III) by combination of UV-visible (UV-Vis) and mass spectrometries and cyclic voltammetry. The acidity constants of the ligand as well as the stability constants of the metal complexes were calculated. The pKa values of 6.58, 11.97 and 13.87 were determined and the following acidity order is proposed 7-OH>5-OH>2'-OH. The best fit between experimental and calculated spectra was obtained assuming the formation of two Cu(II) complexes: [CuL] logbeta=19.34+/-0.05 and [CuL(2)](2-) logbeta=26.4+/-0.10 and three Fe(III) complexes: [FeL(3)](3-) logbeta=44.72+/-0.09, [FeL(2)](-) logbeta=35.32+/-0.08 and [FeL](+) logbeta=19.51+/-0.04. In addition, copper and iron reduction is less favorable in the presence of floranol. These results indicate that floranol can efficiently bind Cu(II) and Fe(III) ions thus preventing their effect on LDL oxidation.     

Synthesis and electrochemical characterisation of new tantalum (V) alkythio phthalocyanines

The synthesis and electrochemical characterisation of octa-pentylthio (4a) and octa-octylthio (4b) - phthalocyaninato tantalum (III) hydroxide are hereby reported. These TaPc complexes absorb in the near infrared region (∼800 nm in dichloromethane). They show good solubility in most common solvents especially non-viscous solvents such as dichloromethane and chloroform. NMR, mass and infrared spectroscopy and elemental analysis confirmed the structures and purity of the synthesised complexes. The cyclic voltammograms (CVs) showed reversible reduction couples and irreversible oxidation peaks. The latter exhibited adsorption behavior. The reduction processes were observed at −0.74 and −1.13 V (versus Ag|AgCl) for 4a, and −0.67, −1.02 and −1.48 V (versus Ag|AgCl) for 4b. Spectroelectrochemistry confirmed one metal reduction, with the rest of the redox processes being centered on the phthalocyanine ring.     

Synthesis and antioxidant properties of diphenylmethane derivative bromophenols including a natural product

Bromination of bis(3,4-dimethoxyphenyl)methanone (5) gave four products (6–9) with mono, di, tri, and tetra Br under different conditions. Reduction and demethylation reactions of product 9 with tetra Br were performed, consecutively and a natural product, 5,5′-methylene bis(3,4-dibrombenzene-1,2-diol) (1), was obtained with a 53% yield. Five derivatives, (13–17) (bromophenols), of 1 were also synthesised. The antioxidant and radical scavenging activities of bromophenols 1 and 13–17 were determined by employing various in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^?), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS^?+), N,N-dimethyl-p-phenylenediamine dihydrochloride radical cation (DMPD^?+), and superoxide anion radical (O₂^?-) scavenging, reducing ability determination by the Fe³⁺-Fe²⁺ and Cu²⁺-Cu⁺ cupric reducing antioxidant capacity (CUPRAC) transformation methods, hydrogen peroxide scavenging, and ferrous ion (Fe²⁺) chelating activities. Moreover, these activities were compared to those of synthetic standard antioxidant compounds such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol, and trolox. The results showed that the synthesised bromophenols had effective antioxidant power.     

Synthesis and anti-CVB3 activity of 4-amino acid derivative substituted pyrimidine nucleoside analogues

Seven novel 4-amino acid derivative substituted pyrimidine nucleoside analogues were designed, synthesized, and tested for their anti-CVB3 activity. Initial biological studies indicated that among these 4-amino acid derivative substituted pyrimidine nucleoside analogues, 4-N-(2′-amino-glutaric acid-1′-methylester)-1-(2′- deoxy-2′-β-fluoro-4′-azido)-furanosyl-cytosine 2 exhibited the most potent anti-CVB activity (IC₅₀ = 9.3 μM). The cytotoxicity of these compounds has also been assessed. The toxicity of compound 2 was similar to that of ribavirin.     

Guest driven self-assembly of a rectangular box from methylaquacobaloxime and 4,4′-biphenyldiboronic acid

We described the guest-induced synthesis of a rectangular host derived from methylaquacobaloxime CH₃Co(dmgH)₂H₂O and 4,4′-biphenyldiboronic acid containing 4,4′-bipyridine (bipy) molecule as guest. The assembly, monitored by a time dependent ¹H NMR experiment, showed that the guest thermodynamically drives the organization of the host. The structural characterization of the complex evidenced a centrosymmetric rectangular box having two biphenyldiboronate units and a central 4,4′-bipyridine spacer connecting the cobaloxime units (1). The spacers have coplanar rings, being negligible the tilt angle around the central C-C bond. The molecular structure of 1 and of the dinuclear complex [CH₃Co(dmgH)₂]₂(bipy) indicates close comparable intermetallic distance for the rigid bipy bridge and a coplanar arrangement of the cobaloxime moieties that facilitates the formation of the molecular box. The other tested ditopic ligands L (α,α′-diamino-p-xylene and 1,6-diaminohexane) used in this study allowed only a partial assembly. These derivatives and the related dinuclear complexes [CH₃Co(dmgH)₂]₂(L), which were synthesized with the aim to obtain further insights about the formation of the molecular boxes, were also characterized by X-ray structural analysis. The structures of [CH₃Co(dmgH)₂]₂(L), beside the expected flexibility of L, indicate not facing cobaloxime moieties. CV measurements suggest the formation of dinuclear non organometallic Co(II) and Co(I) species after the first reduction for all the dinuclear compounds that are stable in solution. For 1 no electronic coupling is shown, in spite of coplanar conformation of the 4,4′-bipyridine rings.     

Synthesis, chemical- and electrochemical properties of ruthenium(II) complexes bearing 2,6-bis(2-naphthyridyl)pyridine

Ruthenium complexes with a terpyridine-analogous ligand, 2,6-bis(2-naphthyridyl)pyridine (bnp), have been synthesized and their chemical and electrochemical properties investigated. The structures of [Ru(bnp)(tpy)](PF₆)₂ (1) and [Ru(bnp)₂](PF₆)₂ (2) were determined by the X-ray structure analysis. The bnp localized redox potentials of 1 and 2 showed significant positive shift by 260-290 mV relative to the analogous Ru-terpyridine complexes.     

Antidyslipidemic and antioxidant activity of an unusual amino acid (2-amino-5-hydroxyhexanoic acid) isolated from the seeds of Crotalaria juncea

In continuation of our drug discovery programme on Indian medicinal plants, we isolated an unusual amino acid, i.e. 2-amino-5-hydroxyhexanoic acid (1) from the seeds of Crotalaria juncea. The 2-amino-5-hydroxyhexanoic acid (1) showed dose dependent lipid lowering activity in the in vivo experiments and also showed good in vitro antioxidant activity. The cyclized compound, 3-amino-6-methyltetrahydro-2H-pyran-2-one (2) showed better lipid lowering and antioxidant profile than the parent compound 1.     

Synthesis and antioxidant activities of novel 4-Schiff base-7-benzyloxy-coumarin derivatives

4-Schiff base-7-benzyloxy-coumarins 5a(1)-5h(2) and its derivative 6 were designed and synthesized based on the 7-benzyloxy-coumarin structure as novel antioxidants. The in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 5b(1), 5d(1), 5f(1), 5f(2), 5g(1) and 5g(2), and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) cation (ABTS(+)) radical scavenging activities of compounds 5a(1), 5b(1), 5c(1), 5c(2), 5d(1), 5e(1), 5e(2), 5f(2), 5g(1), 5g(2) and 5h(1) were better than that of the commercial antioxidant butylated hydroxytoluene (BHT), while the superoxide anion radical scavenging activities of 5a(2) and 5g(2) were stronger than that of the commercial antioxidant butylated hydroxyanisole (BHA), and the hydroxyl radical scavenging activity of 5e(1) was much better than that of the common antioxidant ascorbic acid.     

Analysis of salicylic acid in willow barks and branches by an electrochemical method

An electrochemical method for measuring free salicylic acid (SA) was optimized and used to detect its content in barks and branches of thirteen Salix species. We utilized square wave voltammetry method in combination with pencil lead, the detection limit of which was 1.7 ng/ml of salicylic acid. The highest contents of free SA were observed in the bark of S. laponum (3.0 mg/g fr wt) and in the branches of S. purpurea, cv. Nana (2.1 mg/g fr wt) and S. planifolia (2.2 mg/g fr wt). The technique utilized for determination of SA in willow tissues has a much broader dynamic range and lower limit of detection in comparison to both linear sweep and cyclic voltammetry because of its efficient discrimination of capacitance current. Published in Russian in Fiziologiya Rastenii, 2007, Vol. 54, No. 4, pp. 623–628. The text was submitted by the authors in English.     

Comparative electrochemical study on monolignols and dimers relevant for the comprehension of the lignification process

The objective of the present study is to complete previous electrochemical studies on coniferyl alcohol analogs by focusing on its dimers to further elucidate the lignification process, in order to distinguish between steric and electronic factors that inhibit oxidation. The results demonstrated that monolignols exhibit lower oxidation potential values than dimers and the β-O-4 dimer exhibited a quite peculiar behavior allowing two-electron oxidation. Moreover, we noticed that the pH turned out to affect the redox potential values. Phenol/phenol cation radical couples had a significantly higher potential than the corresponding phenate/phenoxy radical couple. These results emphasize the importance of understanding the specificities of in planta lignin growth and structure.

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Mechanistic study of the oxidation of caffeic acid by digital simulation of cyclic voltammograms

The oxidation mechanism of caffeic acid (CAF) has been studied by means of cyclic voltammetry with the plastic formed carbon or glassy carbon electrode. CAF gives a well-developed two-electron reversible wave in acidic media, whereas it shows an irreversible behavior, i.e., a decrease of the rereduction peak, in less acidic media, suggesting that the oxidation of CAF follows an irreversible chemical reaction(s). Digital simulation analyses based on different oxidation mechanisms have been performed for the voltammograms obtained with the GC electrode in 1:1 (v/v) water:ethanol solutions. The results clearly show that the seeming two-electron oxidation of CAF occurs stepwise via one-electron processes, each of which follows an irreversible chemical reaction. It has also been suggested that the semiquinone radical as an intermediate of the one-electron oxidation should play an important role in the oxidation reaction. Evaluations of the rate constants for the chemical reactions have further suggested that the chemical reactions are dimerization reactions.